P435: ANALYSIS OF MYELOBLAST IMMUNOPHENOTYPE PROFILE IN ACUTE MYELOID LEUKAEMIA AS PREDICTOR FOR CLINICAL OUTCOME
Authors: M. Sobas, M. Nowak, D. Szymczak, I. Andrasiak, T. Wróbel
Journal: HemaSphere (2022)

Background: The European LeukemiaNet (ELN) classification, is currently widely accepted risk stratification of acute myeloid leukaemia (AML). ELN stratification is based on genetic abnormalities and divides AML in low, intermediate and high risk groups. However, the outcome of AML patients, even within one classified group may be different. Flow cytometry analysis of blast cells play an essential role in diagnosis of AML, but the prognostic value of particular antigen expression is still unknown. Aims: The aim of this study was to investigate the prognostic impact of the immunophenotype of blast cells. Methods: We performed a retrospective analysis on 146 AML patients (aged 21-65) who were diagnosed and treated with intensive chemotherapy between 2017-2020. Allo-HSCT recipients were labelled TPL1, the others - TPL0. Patients with acute promyelocytic leukaemia were excluded from the study. Quantitative value (%) of particular antigen (CD2, CD4, CD7, CD9, CD11b, CD11c, CD13, CD14, CD15, CD16, CD19, CD25, CD33, CD34, CD36, CD38, CD41, CD45, CD56, CD61, CD64, CD65, CD71, CD73, CD96 CD117, CD123, HLA-DR) expression was collected. ELN classification at diagnosis, cytogenetic, mutational status (FLT3-ITD, FLT3-TKD, NPM1, CEBPA, CBFB-MYH11, RUNX1-RUNX1T1) and outcome (complete remission (CR), primary resistance, relapse after achieving CR were recorded). Categorical variables were presented as frequencies with percentages, median and interquartile range (IQR) were used to describe continuous variables. Non-normally distributed variables were analysed using Mann Whitney test and Kruskal-Wallis test. The Kaplan-Meier method and Cox proportional-hazards model were used to estimate time-to-event variables and determine hazard ratio (HR). All statistical tests were two-tailed with the significance level set at α=0,05. The study was performed in accordance with the Declaration of Helsinki. Results: The baseline characteristics of the patients are presented in a table. The median age at diagnosis was 54 (aged 21-65). CR rate was 73%. The median follow up of 146 AML was 443 days. The median value of HLA-DR of relapsed (n=31, 21%) vs non-relapsed AML (n=115, 79%) was higher: 100 (90-100) vs 90 (67-99); p=0.006. There was no relationship between the HLA-DR expression (%) and ELN risk (p=0.705) nor mutational status (p>0.05). The primary resistance was more common in patients with higher CD34 and lower CD38 levels. The median value of CD34 in resistant AML vs those who achieved CR was 93% (22-99) vs 47% (0-91); p=0.017 and the median value of CD38 was 61% (31-93) vs 93% (83-98); p=0.011. The median CD34 value was significantly higher in the adverse vs favourable ELN-group: 79% (18-96) vs 2% (0-69), respectively (p=0.001) while the median CD38 value was significantly higher in the favourable vs adverse ELN-group, 96% (88-99) vs 86% (58-96), respectively, (p=0.005). Improved EFS was reported for decrease of HLA-DR (HR=1.01; p=0.049) and increase of CD38 (HR=0.99; p=0.046) among TPL0 patients. These variables are borderline during OS prediction for TPL0 - HLA-DR (HR=1.01; p=0.081) and CD38 (HR=0.99; p=0.051). Image:Summary/Conclusion: Together with genetic mutations, immunophenotyping could be an equivalent component of risk assessment. The levels of CD34 and CD38 turned out to modify the first line treatment response and correlate with the ELN stratification. Higher percentage of CD34 and lower of CD38 may characterise refractory to standard intensive therapy AML, while higher HLA-DR may proceed relapse. Further, analyses, on prospective trials, should be conducted to confirm these correlations.